Biosynthetic mapping of the complete details of indole alkaloid biosynthesis in V. rosea and related species will be studied using sequential isolation and feeding of intermediates to germinating seeds. The rearrangements and transformations from tryptophan and geraniol up to the most complex, dimeric oncolytic alkaloids such as VLB will be examined. The same mechanisms which are operating in vivo will be applied to the economical total synthesis of a wide range of alkaloids, hitherto only available in small amounts for biological activity evaluation. Carbon-13 NMR will be used in depletion experiments (12CO2). Cell-free biosynthesis and the enzymology of the dimerization process will be examined, using tissue cultures.